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At least 1,009 records · Page 56Linked to original sources
PubMed2005

Nonlinear acoustic scattering by a partially closed surface-breaking crack.

A theoretical model describing the nonlinear scattering of acoustic waves by surface-breaking cracks with faces in partial contact is presented. The nonlinear properties of the crack are accounted for by suitable boundary conditions that are derived from micromechanical models of the dynamics of elastic rough surfaces in contact. Both linear and nonlinear responses of the crack are shown to be largest for a shear vertical wave incident on the surface containing the crack at an angle just above the critical angle for longitudinal waves. These findings question the fitness for the purpose of a conventional inspection method, which utilizes shear vertical waves at 45 degrees of incidence to search for surface-breaking cracks in many engineering components. For angles of incidence proximal to the critical angle of longitudinal waves, the efficiency of the second harmonic's generation appears to be the highest. Thanks to the increased sensitivity to surface-breaking cracks, this configuration seems to offer a solution to the localization problem, a task that has eluded nonlinear techniques operating under other circumstances. Finally, this model suggests a simple interpretation of the highly localized nonlinear response of delaminations in composite materials.

Journal Article↗
PubMed2003

Rethinking sedation and agitation management in critical illness.

OBJECTIVE: To examine difficulties in sedation management in the critically ill patient and explore how a semi automated sedation controller can improve agitation control. To present recent work on measurements of agitation, dynamic systems modelling and control of patient agitation response. DATA SOURCES: Articles and peer-reviewed studies identified through a PUBMED search and selected original works from the biomedical engineering literature of relevance to agitation control and management. SUMMARY OF REVIEW: Over-sedation has an adverse impact on intensive care resources. Interventions to constrain sedation delivery through development of protocols or regular cessation of infusions result in reduction in resource utilisation, but have not significantly addressed existing difficulties in agitation control. We develop a paradigm in which control of agitation in critically ill patients becomes the primary objective of sedation management. This principle is central to the function of a nurse-managed semi-automated sedation delivery device. The clinical application of this device using subjective assessments of agitation is presented. A framework for the development of improved automated sedation delivery systems using objective measurements of agitation and control, based on agitation feedback, is described. Using dynamic systems modelling and a simulated nurse, a bolus-driven approach significantly reduced agitation and minimised drug utilisation. This result challenges the current practice of sedating patients using continuous infusions. CONCLUSIONS: A simple computerised interface with an algorithm that continually reduces the infusion rate in the absence of agitation has successfully been introduced into clinical practice. Nursing staff reported high levels of satisfaction with this device and it has enabled detailed data on patterns of sedation administration to be extracted for analysis. This data has been used to validate a model of the fundamental agitation-sedation dynamics.

Journal Article↗
PubMed2000

Intravascular ultrasound-guided interventions in coronary artery disease: a systematic literature review, with decision-analytic modelling, of outcomes and cost-effectiveness.

BACKGROUND: Intravascular ultrasound (IVUS) is the generic name for any ultrasound technology used in vivo within the blood vessels. More specifically, intracoronary ultrasound enables imaging of the coronary arteries from within the lumen. This review concentrates on the role of intracoronary ultrasound as an adjunct to interventional cardiology. OBJECTIVES: (1) To identify the literature on IVUS for guiding coronary interventions, and to synthesise evidence about outcomes compared with outcomes when IVUS guidance has not been used. (2) To use this evidence, together with other information about costs and outcomes, to model the cost effectiveness of IVUS guidance. (3) To synthesise the evidence on the reproducibility of measurements of cross-sectional area made using IVUS. METHODS DATA SOURCES: (1) Electronic searches of MEDLINE, EMBASE, Science Citation Index, Index to Scientific and Technical Proceedings, Engineering Compendex, Engineering Page One, Cochrane Library, Inside (British Library), 1990-98. (2) Contacting experts and centres of expertise, 1990-99. (3) Internet search, 1990-99. METHODS STUDY SELECTION: Studies of IVUS-guided coronary interventions performed on humans were included in the review. Non-English language studies were also included when they covered IVUS-guided stenting or angioplasty. Control evidence regarding outcomes without IVUS guidance was sought only from randomised controlled trials (RCTs). Studies investigating the reproducibility of measurements of cross-sectional area were included only if the results were expressed in terms of the mean and standard deviation of paired differences. METHODS DATA EXTRACTION: Checklists that covered study details, patient characteristics and results were completed independently by three reviewers. Consensus was reached on any disagreements. Local data were gathered on the costs of IVUS-guided stenting. METHODS DATA SYNTHESIS: Overall event rates were calculated by pooling patient results from the included studies. A decision-analytic model was used to combine information from the literature with cost estimates, in order to predict cost-effectiveness in terms of cost per restenosis event avoided by the use of IVUS guidance. The analysis was performed from the perspective of the healthcare provider. Sensitivity analysis was undertaken. A simple extrapolation was made to long-term outcome so that cost-utility (using quality-adjusted life years (QALYs)) could be estimated. The minimum detectable change in cross-sectional area was estimated from the reproducibility results. RESULTS: Only one study on IVUS-guided angioplasty satisfied the inclusion criteria, and there were no studies on IVUS-guided atherectomy or other IVUS-guided interventions that satisfied the inclusion criteria. Of the 15 articles on IVUS-guided stenting that satisfied the inclusion criteria, seven presented data on outcomes at 6 months post-intervention. The angiographic restenosis rate was 16 +/- 1%. This compared with 24 +/- 2% derived from five articles on stenting without IVUS guidance. Data for follow-up periods longer than 6 months were presented in only two studies. Data from a total of five studies were included in the decision-analytic model. The cost per restenosis event avoided was 1545 pound sterling. After extrapolation to long-term outcome, the calculated cost per QALY was 6438 pound sterling. The baseline QALY gain was only 0.03 years. Sensitivity analysis resulted in large differences between the best- and worst-case scenarios, for example, from a saving of 5000 pound sterling to a cost of 24,000 pound sterling restenosis event avoided. The smallest changes in cross-sectional area that could be measured were 1.6 mm2 by a single observer and 1.9 mm2 by different observers. CONCLUSIONS: Implications for healthcare: The evidence available is too weak for there to be any reliable implications for clinical practice. (ABSTRACT TRUNCATED)

Algorithms↗
PubMed2003

Living artificial heart valve alternatives: a review.

Conventional replacement therapies for heart valve disease are associated with significant drawbacks. The field of tissue engineering has emerged as an exciting alternative in the search for improved heart valve replacement structures. One of the principles behind this concept is the transplantation of living elements, embedded in a suitable scaffold material, to the diseased site where the structure becomes integrated with patients' tissue to restore natural function. Significant progress has been made in the last ten years in the development of a living artificial heart valve alternative (LAHVA), with the identification of potential replacement sources for valve cells, scaffolds to maintain the cells in a three-dimensional environment, and signals to promote tissue development. This review addresses the need for a tissue-engineered alternative to current prostheses and provides a detailed account of normal heart valve structure--the blueprint for LAHVA fabrication. The research efforts to create a viable LAHVA, including recent developments, are discussed. Particular attention is focused on the choice of cell source for LAHVA construction, the use of biodegradable natural and synthetic polymeric scaffolds as extracellular matrix derivatives, and exogenous stimulation of tissue growth. The critical challenges involved in LAHVA development and possible future areas of investigation are also discussed.

Absorbable Implants↗
PubMed2002

Quality of web-based medical information on stable COPD: comparison of non-commercial and commercial websites.

The Internet provides an easy and accessible way to deliver medical information about the management of various diseases, both to practitioners and to their patients. As there is no control over who posts information on the Web, there is a risk that the interests of the web producer may bias the quality of information. The quality of medical information on the management of chronic obstructive pulmonary disease (COPD) on the Internet was evaluated, comparing non-commercial and commercial websites. An internet search was conducted to locate relevant websites using a metasearch engine. The quality of websites was scored on a scale of 0-10, based on three items about the credibility of the site and seven items about the accuracy of the information provided by the site. Quality differences between commercial and non-commercial websites were explored. The search revealed 23 relevant websites (12 noncommercial and 11 commercial). The overall quality of non-commercial websites was better than that of commercial websites (median score 7 vs. 4, P = 0.01). Compared to commercial sites, non-commercial websites more often provided information about cessation of smoking (100% vs. 64%, P = 0.03), preventative influenza vaccinations (42% vs. 9%, P = 0.07) and use of long-term oxygen therapy (92% vs. 45%, P = 0.02). Among websites providing information on COPD, commercial sites were much more likely to be of poorer quality compared to sites of non-commercial organizations. In particular, commercial sites do not provide information about simple preventative treatments. There is a need to be vigilant about the quality of health information about COPD on the Internet.

Commerce↗
PubMed2000

Use of plasma glow for surface-engineering biomolecules to enhance bloodcompatibility of Dacron and PTFE vascular prosthesis.

The search for a nonthrombogenic material having patency to be used for small diameter vascular graft applications continues to be a field of extensive investigation. The purpose of the present study was to examine whether surface modification of polytetra fluoroethylene (PTFE, Teflon) and polyethylene-terephthalate (Dacron) vascular grafts might extend graft biocompatibility without modifying the graft structure. A series of surface coatings were prepared by modifying the argon plasma-treated PTFE and Dacron grafts with collagen IV and laminin and subsequently immobilizing bioactive molecules like PGE1, heparin or phosphatidyl choline via the carbodiimide functionalities. Surface analysis by Fourier transform infrared spectroscopy-attenuated total reflectance revealed the presence of new functional groups on the modified graft surfaces. In vitro studies showed that fibrinogen adsorption and platelet adhesion on modified grafts were significantly reduced. This study proposes that surface grafting of matrix components (collagen-type IV and laminin) and subsequent immobilization of bioactive molecules (PGE1, heparin or phosphatidyl choline) changed the surface conditioning of vascular grafts and subsequently improved their biocompatibility. However, more detailed in vivo studies are needed to confirm these observations.

Biocompatible Materials↗
PubMed1997

Correlation of the enzyme activities of Bacillus stearothermophilus lactate dehydrogenase on three substrates with the results of molecular dynamics/energy minimization conformational searching.

Current methods for reengineering enzyme substrate specificities rely heavily on the use of static x-ray crystallographic models. In this article we detail the use of a molecular mechanics approach for suggesting regions of Bacillus stearothermophilus L-lactate dehydrogenase (EC 1.1.1.27) involved in substrate specificity, and hence areas of interest for protein engineers. The approach combines molecular dynamics with energy minimization (MD/EM) to search the conformational space available to a 15-A sphere of the ternary complex centered on the catalytic histidine. The search is carried out by calculating a 30-ps dynamics trajectory at 300 K and minimizing structures at 1-ps intervals. The protocol has been performed on 14 systems containing different combinations of substrate and mutant/wt LDH. In order to discover which interactions are important in defining substrate specificity, eight conformational parameters representing substrate-active site interactions were measured in each of the 420 minimized structures. These parameters were then compared to the measured catalytic activity of the protein-substrate combinations. These comparisons show that arginine 109 orientation is a major determining factor in LDH specificity. Using this methodology it is possible to estimate the catalytic activity of proteins of varied sequence by computer simulation before synthesis.

Catalysis↗
PubMed2006

Through the interaction of neutral and adaptive mutations, evolutionary search finds a way.

An evolutionary system that supports the interaction of neutral and adaptive mutations is investigated. Experimental results on a Boolean function and needle-in-haystack problems show that this system enables evolutionary search to find better solutions faster. Through a novel analysis based on the ratio of neutral to adaptive mutations, we identify this interaction as an engine that automatically adjusts the relative amounts of exploration and exploitation to achieve effective search (i.e., it is self-adaptive). Moreover, a hypothesis to describe the search process in this system is proposed and investigated. Our findings lead us to counter the arguments of those who dismiss the usefulness of neutrality. We argue that the benefits of neutrality are intimately related to its implementation, so that one must be cautious about making general claims about its merits or demerits.

Algorithms↗
PubMed2003

Automated design of specificity in molecular recognition.

Specific protein-protein interactions are crucial in signaling networks and for the assembly of multi-protein complexes, and represent a challenging goal for protein design. Optimizing interaction specificity requires both positive design, the stabilization of a desired interaction, and negative design, the destabilization of undesired interactions. Currently, no automated protein-design algorithms use explicit negative design to guide a sequence search. We describe a multi-state framework for engineering specificity that selects sequences maximizing the transfer free energy of a protein from a target conformation to a set of undesired competitor conformations. To test the multi-state framework, we engineered coiled-coil interfaces that direct the formation of either homodimers or heterodimers. The algorithm identified three specificity motifs that have not been observed in naturally occurring coiled coils. In all cases, experimental results confirm the predicted specificities.

Algorithms↗
PubMed1996

A rapid and effective procedure for screening protease mutants.

We describe a simple and effective procedure to screen for active proteases among a large number of mutants. First, the mutants are genetically tested by the protease activity produced in the periplasm of transformed bacteria which supplies the cells with a nitrogen source by hydrolyzing a protein applied to plates. Then a less sensitive activity staining and an X-ray film digestion assay are used to verify and estimate the activity of the mutants that proved to be positive in the first step. Depending essentially on the level of periplasmic protease activity, the method can detect both the activity and the stability of the expressed enzymes. We calibrated the method with transformants that produce wild-type trypsin, chymotrypsin and trypsin mutants of known activity. Using this method we found two active revertants of the inactive Asn102 trypsin mutant, by screening approximately 4.4 x 10(4) random mutants that were generated by the polymerase chain reaction on a cDNA fragment. This procedure should be useful in searching for proteases of novel specificity and/or reaction chemistry engineered by random mutagenesis, and also for in vitro evolution studies.

Amino Acid Sequence↗
PubMed2005

The value of short amino acid sequence matches for prediction of protein allergenicity.

Typically, genetically engineered crops contain traits encoded by one or a few newly expressed proteins. The allergenicity assessment of newly expressed proteins is an important component in the safety evaluation of genetically engineered plants. One aspect of this assessment involves sequence searches that compare the amino acid sequence of the protein to all known allergens. Analyses are performed to determine the potential for immunologically based cross-reactivity where IgE directed against a known allergen could bind to the protein and elicit a clinical reaction in sensitized individuals. Bioinformatic searches are designed to detect global sequence similarity and short contiguous amino acid sequence identity. It has been suggested that potential allergen cross-reactivity may be predicted by identifying matches as short as six to eight contiguous amino acids between the protein of interest and a known allergen. A series of analyses were performed, and match probabilities were calculated for different size peptides to determine if there was a scientifically justified search window size that identified allergen sequence characteristics. Four probability modeling methods were tested: (1) a mock protein and a mock allergen database, (2) a mock protein and genuine allergen database, (3) a genuine allergen and genuine protein database, and (4) a genuine allergen and genuine protein database combined with a correction for repeating peptides. These analyses indicated that searches for short amino acid sequence matches of eight amino acids or fewer to identify proteins as potential cross-reactive allergens is a product of chance and adds little value to allergy assessments for newly expressed proteins.

Allergens↗
PubMed2005

Crystallization, X-ray diffraction analysis and phasing of 17beta-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus.

17beta-Hydroxysteroid dehydrogenase from the filamentous fungus Cochliobolus lunatus (17beta-HSDcl) is an NADP(H)-dependent enzyme that preferentially catalyses the oxidoreduction of oestrogens and androgens. The enzyme belongs to the short-chain dehydrogenase/reductase superfamily and is the only fungal hydroxysteroid dehydrogenase known to date. 17beta-HSDcl has recently been characterized and cloned and has been the subject of several functional studies. Although several hypotheses on the physiological role of 17beta-HSDcl in fungal metabolism have been formulated, its function is still unclear. An X-ray crystallographic study has been undertaken and the optimal conditions for crystallization of 17beta-HSDcl (apo form) were established, resulting in well shaped crystals that diffracted to 1.7 A resolution. The space group was identified as I4(1)22, with unit-cell parameters a = b = 67.14, c = 266.77 A. Phasing was successfully performed by Patterson search techniques. A catalytic inactive mutant Tyr167Phe was also engineered, expressed, purified and crystallized for functional and structural studies.

17-Hydroxysteroid Dehydrogenases↗
PubMed2003

Epileptic seizure prediction and control.

Epileptic seizures are manifestations of epilepsy, a serious brain dynamical disorder second only to strokes. Of the world's approximately 50 million people with epilepsy, fully 1/3 have seizures that are not controlled by anti-convulsant medication. The field of seizure prediction, in which engineering technologies are used to decode brain signals and search for precursors of impending epileptic seizures, holds great promise to elucidate the dynamical mechanisms underlying the disorder, as well as to enable implantable devices to intervene in time to treat epilepsy. There is currently an explosion of interest in this field in academic centers and medical industry with clinical trials underway to test potential prediction and intervention methodology and devices for Food and Drug Administration (FDA) approval. This invited paper presents an overview of the application of signal processing methodologies based upon the theory of nonlinear dynamics to the problem of seizure prediction. Broader application of these developments to a variety of systems requiring monitoring, forecasting and control is a natural outgrowth of this field.

Algorithms↗
PubMed2003

The postural effects of load carriage on young people--a systematic review.

BACKGROUND: Spinal pain in young people is a significant source of morbidity in industrialised countries. The carriage of posterior loads by young people has been linked with spinal pain, and the amount of postural change produced by load carriage has been used as a measure of the potential to cause tissue damage. The purpose of this review was to identify, appraise and collate the research evidence regarding load-carriage related postural changes in young people. METHODS: A systematic literature review sought published literature on the postural effects of load carriage in young people. Sixteen databases were searched, which covered the domains of allied health, childcare, engineering, health, health-research, health-science, medicine and medical sciences. Two independent reviewers graded the papers according to Lloyd-Smith's hierarchy of evidence scale. Papers graded between 1a (meta-analysis of randomised controlled trials) and 2b (well-designed quasi-experimental study) were eligible for inclusion in this review. These papers were quality appraised using a modified Crombie tool. The results informed the collation of research evidence from the papers sourced. RESULTS: Seven papers were identified for inclusion in this review. Methodological differences limited our ability to collate evidence. CONCLUSIONS: Evidence based recommendations for load carriage in young people could not be made based on the results of this systematic review, therefore constraining the use of published literature to inform good load carriage practice for young people.

Adolescent↗
PubMed1998

Occupational exposure to laser surgery generated air contaminants.

The objective of the review is to show that scientific evidence is lacking on the safety of laser-generated air contaminants. Further research and data collection are necessary to characterize the potential dangers associated with exposures of health care professionals to laser generated air contaminants. The article is a review of existing scientific evidence in the area of exposure risks to health care professionals. A careful search of the scientific literature both in medicine and engineering was performed, as well as contact with experts from laser standards advisory sources. These sources include: International Laser Safety Conference, National Institute of Occupational Safety and Health, American National Standard Institute, Laser Safety Institute and Rockwell Laser Industries. The review includes articles in the literature documenting cases of over-exposures to contaminants while using a class IV laser, the same class laser used in surgery. Several studies of case reports of laser-generated air contaminants from cutting on human and animal tissues are included. Articles and guidelines on this subject of laser-generated contaminants from the above listed sources were used in writing this review. The review indicates that lasers used in surgery are potential occupational health risks.

Air Pollutants, Occupational↗
PubMed1994

GeneQuiz: a workbench for sequence analysis.

We present the prototype of a software system, called GeneQuiz, for large-scale biological sequence analysis. The system was designed to meet the needs that arise in computational sequence analysis and our past experience with the analysis of 171 protein sequences of yeast chromosome III. We explain the cognitive challenges associated with this particular research activity and present our model of the sequence analysis process. The prototype system consists of two parts: (i) the database update and search system (driven by perl programs and rdb, a simple relational database engine also written in perl) and (ii) the visualization and browsing system (developed under C++/ET++). The principal design requirement for the first part was the complete automation of all repetitive actions: database updates, efficient sequence similarity searches and sampling of results in a uniform fashion. The user is then presented with "hit-lists" that summarize the results from heterogeneous database searches. The expert's primary task now simply becomes the further analysis of the candidate entries, where the problem is to extract adequate information about functional characteristics of the query protein rapidly. This second task is tremendously accelerated by a simple combination of the heterogeneous output into uniform relational tables and the provision of browsing mechanisms that give access to database records, sequence entries and alignment views. Indexing of molecular sequence databases provides fast retrieval of individual entries with the use of unique identifiers as well as browsing through databases using pre-existing cross-references. The presentation here covers an overview of the architecture of the system prototype and our experiences on its applicability in sequence analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Prediction of posttranslational modifications using intact-protein mass spectrometric data.

We present a Web-based application that uses whole-protein masses determined by mass spectrometry to identify putative co- and posttranslational proteolytic cleavages and chemical modifications. The protein cleavage and modification engine (PROCLAME) requires as input an intact mass measurement and a precursor identification based on peptide mass fingerprinting or tandem mass spectrometry. This approach predicts mass-modifying events using a depth-first tree search, bounded by a set of rules controlled by a custom-built fuzzy logic engine, to explore a large number of possible combinations of modifications accounting for the experimental mass. Candidates are saved during a search if they are within a user-specified instrument mass accuracy; the total number of possible candidates searched is based on a specified fuzzy cutoff score. Candidates are scored and ranked using a simple probabilistic model. There is generally not enough information in an intact mass measurement to determine a single unique protein characterization; however, the program provides utility by expediting the identification of sets of putative events consistent with the mass data and ranking them for further investigation. This approach uses a simple, intuitive rule base and lends itself to discovery of unannotated posttranslational events. We have assessed the program with both in silico-generated test data and with published data from an analysis of large ribosomal subunit proteins, both from the yeast S. cerevisiae. Results indicate a high degree of sensitivity and specificity in characterizing proteins whose masses resulted from reasonable proteolysis and covalent modification scenarios. The application is available on the web at http://proclame.unc.edu.

Computational Biology↗